In a milestone in mammalian genetic engineering, a team of researchers from the Chinese Academy of Sciences succeeded in creating a viable bipaternal mouse from sperm provided by two male parents. The study, led by Zhi-kun Li, Wei Li, and Qi Zhou, was published in the scientific journal Cell Stem Cell. This achievement represents the first successful creation of adult male-male bipaternal mice.
The researchers focused on overcoming genomic imprinting, a fundamental barrier to unisexual reproduction in mammals. Genomic imprinting is a mechanism that regulates gene expression based on parental origin, requiring every embryo to derive from a male gamete (sperm) and a female gamete (egg). "The unique characteristics of imprinted genes have led scientists to believe that they are a fundamental barrier to unisexual reproduction in mammals," said Qi Zhou, a researcher who has led many advances in assisted reproduction procedures, according to Scientias. "Even when bimaternal or bipaternal embryos are artificially constructed, they do not develop properly and stall at some point during development due to these genes," he added.
In their study, the Chinese scientists used CRISPR/Cas9-based gene editing to target mammal-specific "imprinting genes" that act as a "lock" preventing unisexual reproduction. By modifying 20 key imprinted genes in the genome, they were able to create viable embryos free from genomic imprinting anomalies. These alterations allowed the creation of bipaternal animals that survived to adulthood but are completely sterile and have a lower life expectancy.
The team created 1,081 embryos, of which only 11.8% (29 out of 210) survived to birth, much lower than would normally occur. Not all of the newborns reached adulthood due to developmental defects, and those that did often had shorter lifespans and growth abnormalities. The adult mice were sterile but showed higher cloning efficiency compared to their wild-type counterparts. Despite these challenges, the researchers emphasized that the mere fact that these animals reached adulthood marks a milestone in research.
Li expressed hope that this work will help address a series of limitations in stem cell research and regenerative medicine.
The research team planned to continue studying how modifying imprinted genes can lead to embryos with greater developmental potential and wanted to expand their research to larger animals, such as monkeys. However, they noted that extending the experimental approaches developed in mice to larger animals would require considerable time and effort because the imprinting gene combinations in monkeys differ from those in mice.
According to the researchers, the applications of this technique in human assisted reproduction are not currently possible.
The International Society for Stem Cell Research prohibits editing the heritable genome and using artificial gametes for human reproduction.
Previous attempts to create bipaternal mice had failed because the embryos stopped growing at early stages.
The article was written with the assistance of a news analysis system.